Tag Archives: gastrointestinal tract

Contrast agents used for magnetic resonance imaging, x-ray imaging, ultrasounds, and other imaging technologies are not always kind to the humans ingesting them. So, scientists at the University at Buffalo (also known as the State University of New York at Buffalo) have developed a veggie juice that does the job according to a July 11, 2016 news item on Nanowerk (Note: A link has been removed),

The pigment that gives spinach and other plants their verdant color may improve doctors’ ability to examine the human gastrointestinal tract.

That’s according to a study, published in the journal Advanced Materials (“Surfactant-Stripped Frozen Pheophytin Micelles for Multimodal Gut Imaging”), which describes how chlorophyll-based nanoparticles suspended in liquid are an effective imaging agent for the gut.

The University of Buffalo has provided an illustration of the work,

A new UB-led study suggests that chlorophyll-based nanoparticles are an effective imaging agent for the gut. The medical imaging drink, developed to diagnose and treat gastrointestinal illnesses, is made of concentrated chlorophyll, the pigment that makes spinach green. Photo illustration credit: University at Buffalo.

“Our work suggests that this spinach-like, nanoparticle juice can help doctors get a better look at what’s happening inside the stomach, intestines and other areas of the GI tract,” says Jonathan Lovell, PhD, assistant professor in the Department of Biomedical Engineering, a joint program between UB’s School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB, and the study’s corresponding author.

To examine the gastrointestinal tract, doctors typically use X-rays, magnetic resonance imaging or ultrasounds, but these techniques are limited with respect to safety, accessibility and lack of adequate contrast, respectively.

Doctors also perform endoscopies, in which a tiny camera attached to a thin tube is inserted into the patient’s body. While effective, this procedure is challenging to perform in the small intestine, and it can cause infections, tears and pose other risks.

The new study, which builds upon Lovell’s previous medical imaging research, is a collaboration between researchers at UB and the University of Wisconsin-Madison. It focuses on Chlorophyll a, a pigment found in spinach and other green vegetables that is essential to photosynthesis.

In the laboratory, researchers removed magnesium from Chlorophyll a, a process which alters the pigment’s chemical structure to form another edible compound called pheophytin. Pheophytin plays an important role in photosynthesis, acting as a gatekeeper that allows electrons from sunlight to enter plants.

Next, they dissolved pheophytin in a solution of soapy substances known as surfactants. The researchers were then able to remove nearly all of the surfactants, leaving nearly pure pheophytin nanoparticles.

The drink, when tested in mice, provided imaging of the gut in three modes: photoacoustic imaging, fluorescence imaging and positron emission tomography (PET). (For PET, the researchers added to the drink Copper-64, an isotope of the metal that, in small amounts, is harmless to the human body.)

Additional studies are needed, but the drink has commercial potential because it:

· Works in different imaging techniques.

· Moves stably through the gut.

· And is naturally consumed in the human diet already.

In lab tests, mice excreted 100 percent of the drink in photoacoustic and fluorescence imaging, and nearly 93 percent after the PET test.

“The veggie juice allows for techniques that are not commonly used today by doctors for imaging the gut like photoacoustic, PET, and fluorescence,” Lovell says. “And part of the appeal is the safety of the juice.”

While there are a number of wearable and fashionable pieces of technology that monitor heart rate and breathing, they are all worn on the outside of your body. Researchers are working on an alternative that can be swallowed and will monitor vital signs from within the gastrointestinal tract. I believe this is a prototype of the device,

This type of sensor could make it easier to assess trauma patients, monitor soldiers in battle, perform long-term evaluation of patients with chronic illnesses, or improve training for professional and amateur athletes, the researchers say.

The new sensor calculates heart and breathing rates from the distinctive sound waves produced by the beating of the heart and the inhalation and exhalation of the lungs.

“Through characterization of the acoustic wave, recorded from different parts of the GI tract, we found that we could measure both heart rate and respiratory rate with good accuracy,” says Giovanni Traverso, a research affiliate at MIT’s Koch Institute for Integrative Cancer Research, a gastroenterologist at Massachusetts General Hospital, and one of the lead authors of a paper describing the device in the Nov. 18 issue of the journal PLOS One.

Doctors currently measure vital signs such as heart and respiratory rate using techniques including electrocardiograms (ECG) and pulse oximetry, which require contact with the patient’s skin. These vital signs can also be measured with wearable monitors, but those are often uncomfortable to wear.

Inspired by existing ingestible devices that can measure body temperature, and others that take internal digestive-tract images, the researchers set out to design a sensor that would measure heart and respiratory rate, as well as temperature, from inside the digestive tract.

The simplest way to achieve this, they decided, would be to listen to the body using a small microphone. Listening to the sounds of the chest is one of the oldest medical diagnostic techniques, practiced by Hippocrates in ancient Greece. Since the 1800s, doctors have used stethoscopes to listen to these sounds.

The researchers essentially created “an extremely tiny stethoscope that you can swallow,” Swiston says. “Using the same sensor, we can collect both your heart sounds and your lung sounds. That’s one of the advantages of our approach — we can use one sensor to get two pieces of information.”

To translate these acoustic data into heart and breathing rates, the researchers had to devise signal processing systems that distinguish the sounds produced by the heart and lungs from each other, as well as from background noise produced by the digestive tract and other parts of the body.

The entire sensor is about the size of a multivitamin pill and consists of a tiny microphone packaged in a silicone capsule, along with electronics that process the sound and wirelessly send radio signals to an external receiver, with a range of about 3 meters.

In tests along the GI tract of pigs, the researchers found that the device could accurately pick up heart rate and respiratory rate, even when conditions such as the amount of food being digested were varied.

“The authors introduce some interesting and radically different approaches to wearable physiological status monitors, in which the devices are not worn on the skin or on clothing, but instead reside, in a transient fashion, inside the gastrointestinal tract. The resulting capabilities provide a powerful complement to those found in wearable technologies as traditionally conceived,” says John Rogers, a professor of materials science and engineering at the University of Illinois who was not part of the research team.

Better diagnosis

The researchers expect that the device would remain in the digestive tract for only a day or two, so for longer-term monitoring, patients would swallow new capsules as needed.

For the military, this kind of ingestible device could be useful for monitoring soldiers for fatigue, dehydration, tachycardia, or shock, the researchers say. When combined with a temperature sensor, it could also detect hypothermia, hyperthermia, or fever from infections.

In the future, the researchers plan to design sensors that could diagnose heart conditions such as abnormal heart rhythms (arrhythmias), or breathing problems including emphysema or asthma. Currently doctors require patients to wear a harness (Holter) monitor for up to a week to detect such problems, but these often fail to produce a diagnosis because patients are uncomfortable wearing them 24 hours a day.

“If you could ingest a device that would listen for those pathological sounds, rather than wearing an electrical monitor, that would improve patient compliance,” Swiston says.

The researchers also hope to create sensors that would not only diagnose a problem but also deliver a drug to treat it.

“We hope that one day we’re able to detect certain molecules or a pathogen and then deliver an antibiotic, for example,” Traverso says. “This development provides the foundation for that kind of system down the line.”

MIT has provided a video with two of the researchers describing their work and and plans for its future development,

Note added Nov. 25, 2015 at 1625 hours PDT: US National Public Radio (NPR) has a story on this research. You can find Nov. 23, 2015 podcast (about six minutes) and a series of textual excerpts featuring Albert Swiston, biomaterials scientist at MIT, and Stephen Shankland, senior writer for CNET covering digital technology, from the podcast here.

This is the first time I’ve seen testing of two organs for possible adverse effects from nanoparticles. In this case, the researchers were especially interested in the liver. From an Aug. 12, 2014 news item on Azonano,

Nanoparticles in food, sunscreen and other everyday products have many benefits. But Cornell [University] biomedical scientists are finding that at certain doses, the particles might cause human organ damage.

A recently published study in Lab on a Chip by the Royal Society of Chemistry and led by senior research associate Mandy Esch shows that nanoparticles injure liver cells when they are in microfluidic devices designed to mimic organs of the human body. The injury was worse when tested in two-organ systems, as opposed to single organs – potentially raising concerns for humans and animals.

Anne Ju’s Aug. 11, 2014 article for Cornell University’s Chronicle describes the motivation for this work and the research itself in more detail,

“We are looking at the effects of what are considered to be harmless nanoparticles in humans,” Esch said. “These particles are not necessarily lethal, but … are there other consequences? We’re looking at the non-lethal consequences.”

She used 50-nanometer carboxylated polystyrene nanoparticles, found in some animal food sources and considered model inert particles. Shuler’s lab specializes in “body-on-a-chip” microfluidics, which are engineered chips with carved compartments that contain cell cultures to represent the chemistry of individual organs.

In Esch’s experiment, she made a human intestinal compartment, a liver compartment and a compartment to represent surrounding tissues in the body. She then observed the effects of fluorescently labeled nanoparticles as they traveled through the system.

Esch found that both single nanoparticles as well as small clusters crossed the gastrointestinal barrier and reached liver cells, and the liver cells released an enzyme called aspartate transaminase, known to be released during cell death or damage.

It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential, Esch said. Long-term consequences for organs in proximity could be a concern, she said.

“The motivation behind this study was twofold: one, to show that multi-organ, in vitro systems give us more information when testing for the interaction of a substance with the human body, and two … to look at nanoparticles because they have a huge potential for medicine, yet adverse effects have not been studied in detail yet,” Esch said.

Mary Macleod’s July 3, 2014 article for Chemistry World features a diagram of the two-organ system and more technical details about the research,

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

HepG2/C3A cells were used to represent the liver, with the intestinal cell co-culture consisting of enterocytes (Caco-2) and mucin-producing (HT29-MTX) cells. Carboxylated polystyrene nanoparticles were fluorescently labelled so their movement between the chambers could be tracked. Levels of aspartate transaminase, a cytosolic enzyme released into the culture medium upon cell death, were measured to give an indication of liver damage.

The study saw that single nanoparticles and smaller nanoparticle aggregates were able to cross the GI barrier and reach the liver cells. The increased zeta potentials of these nanoparticles suggest that crossing the barrier may raise their toxic potential. However, larger nanoparticles, which interact with cell membranes and aggregate into clusters, were stopped much more effectively by the GI tract barrier.

The gastrointestinal tract is an important barrier preventing ingested substances crossing into systemic circulation. Initial results indicate that soluble mediators released upon low-level injury to liver cells may enhance the initial injury by damaging the cells which form the GI tract. These adverse effects were not seen in conventional single-organ tests.

While this research is deeply concerning, it should be noted the researchers are being very careful in their conclusions as per Ju’s article, “It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential … Long-term consequences for organs in proximity could be a concern … .”

This is a story about nutraceuticals or, more specifically, about nanotechnology and food according to a Jan. 20, 2014 news item on Azonano,

Food scientist Hang Xiao of the University of Massachusetts Amherst recently received a four-year, $491,220 grant to study the biochemical fate of nanoemulsion-based food delivery systems in the gastrointestinal (GI) tract, hoping to re-shape them and enhance the absorption of beneficial food components encapsulated in delivery systems.

Food biochemists like Xiao believe that if taken up in appropriate amounts and forms, certain food components known as nutraceuticals might benefit human health by providing anti-inflammatory or anti-cancer effects. Nutraceuticals include flavonoids and carotenoids in fruits and vegetables, for example.

This project, supported by the U.S. Department of Agriculture’s National Institute of Food and Agriculture, will focus on manipulating the structure and composition of nano-emulsion delivery systems to modify the fate of encapsulated nutraceuticals in the GI tract to enhance their bioavailability.

“In the last decade, knowledge has been advancing about how to effectively deliver beneficial components in food. This research will allow us to direct the assembly of nano-emulsion droplets to create characteristics that will dictate how they are digested and absorbed,” Xiao explains. “This would be a model for nutraceutical delivery in a wide range of food products. Someday prepared foods may help lower our risk of cancer, for example.”

Specifically, using both cell culture and animal models, Xiao and colleagues will design lipid nanoparticles at three stages: From nano-emulsion droplets containing nutraceuticals, to mixed micelles and finally to chylomicrons. To start this process, digestion physiochemically disassembles nano-emulsion droplets. The resulting chemical components are then assembled into mixed micelles in the small intestine, where epithelial cells called enterocytes take them up. There they are reassembled into chylomicrons and absorbed into blood circulation through the lymph system.

The scientists want to influence the size and composition of chylomicrons, because these characteristics dictate the fate of nutraceuticals encapsulated in the chylomicrons. Certain sizes and compositions are better able to deliver nutraceuticals to the lymph system, which protects nutraceuticals from being cleared by the liver. This will enhance bioavailability of flavonoids and other beneficial compounds to the body, potentially offering health benefits.

“We’re basically utilizing what already happens in our bodies all the time, but introducing food-grade nano-emulsion systems that can influence the nature of mixed micelles as well as chylomicrons,” says Xiao. “It’s safe, it’s all digested and simply delivers beneficial food components to a greater extent than if the system was left alone.”

Given that this falls under my nanotechnology and food classification, I was reminded of a recent panel discussion on the topic held by the UK’s Guardian newspaper, from my Oct. 29, 2013 posting,

There’s no indication as to what the 25 audience members thought about the session although Hilary Sutcliffe of Matter was quoted,

Audience member Hilary Sutcliffe, director of the Matter think tank on responsible innovation, was keen to emphasise the limits of nanotechnology in food. “If we’re really lucky, we might get nanosalt and a couple of nano-encapsulated vitamins that go in products,” she told the panel, describing her disappointment in the progress of nanotechnology in food to date.

Sutcliffe explained that these limited applications are expensive and not that useful: manufacturers would rather just reduce salt content than pay for nanosalt, and vitamins and flavourings do not need to be nano-encapsulated because they can be added to foods at the microscale, rather than at the nano-level, which is one thousand times smaller.

She also suggested that, so far, the possible uses of nanotechnology have only been in Western diets and that people should be realistic about its use for tackling the impending global food crisis. “Nothing about nanotechnology is in relation to anything except Western, expensive foods that are slightly gratuitous and not particularly necessary,” she said, before adding that it is not currently helping to feed the world. “If you are going to talk about feeding the world, be brave, take on GM, let’s have that discussion.”

I was not able to find notice of any US public engagement sessions on the topic of ‘nano and food’. If you know of any such sessions, please do share in the comments section.

Researchers, Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, have stated that ingesting food and beverage (translated by me from the more scientific description) with nanoparticles (at today’s current levels) is unlikely to prove toxic. A June 26, 2013 Inderscience news release on EurekAlert describes the researchers’ research and their conclusions,

Writing in a forthcoming issue of the International Journal of Biomedical Nanoscience and Nanotechnology, researchers have compared existing laboratory and experimental animal studies pertaining to the toxicity of nanoparticles most likely to be intentionally or accidentally ingested. Based on their review, the researchers determined ingestion of nanoparticles at likely exposure levels is unlikely to cause health problems, at least with respect to acute toxicity. Furthermore, in vitro laboratory testing, which often shows toxicity at a cellular level, does not correspond well with in vivo testing, which tends to show less adverse effects.

Ingrid Bergin in the Unit for Laboratory Animal Medicine, at the University of Michigan in Ann Arbor and Frank Witzmann in the Department of Cellular and Integrative Physiology, at Indiana University School of Medicine, in Indianapolis, explain that the use of particles that are in the nano size range (from 1 billionth to 100 billionths of a meter in diameter, 1-100 nm, other thereabouts) are finding applications in consumer products and medicine. These include particles such as nano-silver, which is increasingly used in consumer products and dietary supplements for its purported antimicrobial properties. Nanoparticles can have some intriguing and useful properties because they do not necessarily behave in the same chemical and physical ways as non-nanoparticle versions of the same material.

Nanoparticles are now used as natural flavor enhancers in the form of liposomes and related materials, food pigments and in some so-called “health supplements”. They are also used in antibacterial toothbrushes coated with silver nanoparticles, for instance in food and drink containers and in hygienic infant feeding equipment. They are also used to carry pharmaceuticals to specific disease sites in the body to reduce side effects. Nanoparticles actually encompass a very wide range of materials from pure metals and alloys, to metal oxide nanoparticles, and carbon-based and plastic nanoparticles. Because of their increasing utilization in consumer products, there has been concern over whether these small scale materials could have unique toxicity effects when compared to more traditional versions of the same materials.

Difficulties in assessing the health risks of nanoparticles include the fact that particles of differing materials and shapes can have different properties. Furthermore, the route of exposure (e.g. ingestion vs. inhalation) affects the likelihood of toxicity. The U.S. researchers evaluated the current literature specifically with respect to toxicity of ingested nanoparticles. They point out that, in addition to intentional ingestion as with dietary supplements, unintentional ingestion can occur due to nanoparticle presence in water or as a breakdown product from coated consumer goods. Inhaled nanoparticles also represent an ingestion hazard since they are coughed up, swallowed, and eliminated through the intestinal tract.

Based on their review, the team concludes that, “Ingested nanoparticles appear unlikely to have acute or severe toxic effects at typical levels of exposure.” Nevertheless, they add that the current literature is inadequate to assess whether nanoparticles can accumulate in tissues and have long-term effects or whether they might cause subtle alterations in gut microbial populations. The researchers stress that better methods are needed for correlating particle concentrations used for cell-based assessment of toxicity with the actual likely exposure levels to body cells. Such methods may lead to better predictive value for laboratory in vitro testing, which currently over-predicts toxicity of ingested nanoparticles as compared to in vivo testing.

The researchers focused specifically on ingestion via the gastrointestinal tract which I take to mean that they focused largely on nanoparticles in food (eaten) and liquid (swallowed).

The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.